Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid in the eye, is vital for the normal functioning of the retina. Many of the inflammatory, infectious and other diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed human RPE cell culture system and have used this as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We have focussed our attention on Transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinal and Choroidal neovascularization (CNV), observed during age related macular degeneration (ARMD) and diabetic retinopathy, are the leading causes of visual impairment. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and CNV. Platelet derived growth factors (PDGF) are known to be associated with retinal proliferative and angiogenic disorders such as proliferative vitreoretinopathy (PVR) and age realted macular degeneration (ARMD). PDGF promotes proliferation and migration of fibroblasts, pericytes, smooth muscle, glial and RPE cells. Our studies indicated that TGF-b is a potent inducer of PDGF-AA and PDGF-AB in RPE cells while choroidal fibroblasts(CHF) do not produce PDGF. Receptors for PDGF are highly expressed on CHF but not on RPE. Human recombinant PDGF-isoforms (AA, AB, BB) significantly enhanced CHF proliferation, elongation and migration. In contrast no significant effects on RPE proliferation and migration were observed. These results show that PDGF secreted by RPE cells (stimulated by TGF-b) act on nearby connective tissue cells (fibroblasts) and possibly on vascular pericytes and smooth muscle cells. Consequent promotion of proliferation and migration of these target cells results in the pathogenesis of PVR and CNV in ARMD. Regulation of the expression of PDGF in RPE by TGF-b strongly suggests an important role for TGF-b in neovascularization associated with retinal disorders such as PVR and ARMD.